DESCRIPTION (adapted from the application) My goal is to be an outstanding basic scientist and clinician devoted to investigating the pathogenesis and treatment of immunologically mediated glomerular injury. My training from reputed medical institutions in India and the United States has allowed me to conduct several clinical studies that are now published in peer reviewed journals. My research effort over the past two years was focused on an animal model of complement-independent glomerular injury, and has formed the background for the current research proposal. The intellectually stimulating work environment at Boston Medical Center has opened a new horizon for me, and has inspired me to stay on beyond my nephrology fellowship to learn more about glomerular injury at a cellular and molecular level from leading authorities in the field. Under the guidance of my mentors, I plan to study changes in visceral glomerular epithelial cell (visceral GEC) morphology and permeability noted in-vivo in mice following injection of anti-aminopeptidase A (APA) antibodies, using cultured GECs (in-vitro) in the following manner: Specific Aim 1: We will first identify proteins that play a role in APA-mediated injury in cultured GECs by co-precipitating them with anti-APA antibodies. Antibodies to these putative proteins have applications in Specific Aims 2 and 3. Specific Aim 2: We will identify alterations in cell-matrix contact, cell-cell contact and cell polarity following sub-lethal injury with anti-APA. We will also study changes induced by antibodies against APA and its putative associated proteins in the distribution of APA and its associated proteins in vitro and in vivo. Specific Aim 3: We will study the impact on GEC monolayer permeability of appropriate factors from Specific Aims 1 and 2 and others that upregulate the expression of APA, followed by studies on the intracellular transport of APA during sub-lethal injury and recovery. Overall, our characterization of APA-mediated cell injury and its effects on GEC-permeability will help us understand the in-vivo observations mentioned above. This project allows me to learn new skills at three different labs that have access to state-of-the-art technology, and will facilitate my transition towards becoming an independent investigator.